Hox genes are fundamental components of embryonic patterning and morphogenesis with expression persisting into adulthood. They are also implicated in the development of diseases, particularly neoplastic transformations. The tight spatio-temporal regulation of Hox genes in concordance with embryonic patterning is an outstanding feature of these genes. In this review we have systematically analyzed Hox functions within the stem/progenitor cell compartments and asked whether their temporo-spatial topography is retained within the stem cell domain throughout development and adulthood. In brief, evidence support involvement of Hox genes at several levels along the stem cell hierarchy, including positional identity, stem cell self-renewal, and differentiation. There is also strong evidence to suggest a role for Hox genes during neoplasia. Although fundamental questions are yet to be addressed through more targeted and high- throughput approaches, existing evidence suggests a central role for Hox genes within a continuum along the developmental axes persisting into adult homeostasis and disease.